Purpose: To determine whether tenascin-C levels are elevated in the vitreous of patients with proliferative vitreoretinopathy (PVR). Methods: We assayed tenascin-C levels in vitreous samples of 110 consecutive patients with PVR (30 eyes), rhegmatogenous retinal detachment (RRD; 32 eyes), and macular hole or idiopathic epiretinal membrane (controls, 48 eyes) using an enzyme-linked immunosorbent assay. Results: Vitreous levels of tenascin-C (median [range]) were significantly greater in PVR (845.0 ng/ml [411.0–1,050.0]) than in RRD (21.9 ng/ml [13.2–127.0]) and in the controls (18.0 ng/ml [9.9–199.0]) (p < 0.0001). Conclusion: The results indicate the possibility that tenascin-C is involved in the pathogenesis of PVR.